The most common type of animal retroviruses are classified as C-type particles. Five of the receptors for various C type retroviruses have been cloned. Two of these receptors, the receptor for amphotropic murine leukemia virus, (A-MuLV) and the receptor for gibbon ape leukemia virus (GALV) are found on a wide variety of mammalian cells, including most types of human cells where they normally function as phosphate transporters. It is now apparent that other C-type retroviruses utilize these receptors for entry into human cells. The discovery that a number of diverse retroviruses are able to use similar phosphate transporters to infect human cells afforded the opportunity to study common mechanisms these viruses employ to infect human cells and at the same time improve the efficiency of retroviral mediated therapeutic gene delivery to human cells. Three specific aspects of retroviral entry have been addressed: 1) We have identified regions within the GALV receptor that interact with specific viruses. 2) We have determined the regions within the 10A1 and FeLV B viral envelope that are required for targeting the virus to GALV receptor bearing cells. 3) We have initiated the characterization of accessory factors that contribute to efficient retroviral entry such as co-receptors or cell factors involved in the post-virus binding events of viral entry. Understanding the mechanism of retrovirus receptor interaction and entry should further improve the efficiency of retroviral mediated gene transfer.